Osteogenic Activities of Trifolirhizin as a Bioactive Compound for the Differentiation of Osteogenic Cells.
Plant extracts are widely used as traditional medicines. Sophora flavescens Aiton-derived natural compounds exert various beneficial effects, such as anti-inflammatory, anticancer, antioxidant, and antiregenerative activities, through their bioactive compounds, including flavonoids and alkaloids. In the present study, we investigated the biological effects of an S. flavescens-derived flavonoid, trifolirhizin (trifol), on the stimulation of osteogenic processes during osteoblast differentiation. Trifol (>98% purity) was successfully isolated from the root of S. flavescens and characterized. Trifol did not exhibit cellular toxicity in osteogenic cells, but promoted alkaline phosphatase (ALP) staining and activity, with enhanced expression of the osteoblast differentiation markers, including Alp, ColI, and Bsp. Trifol induced nuclear runt-related transcription factor 2 (RUNX2) expression during the differentiation of osteogenic cells, and concomitantly stimulated the major osteogenic signaling proteins, including GSK3β, β-catenin, and Smad1/5/8. Among the mitogen-activated protein kinases (MAPKs), Trifol activated JNK, but not ERK1/2 and p38. Trifol also increased the osteoblast-mediated bone-forming phenotypes, including transmigration, F-actin polymerization, and mineral apposition, during osteoblast differentiation. Overall, trifol exhibits bioactive activities related to osteogenic processes via differentiation, migration, and mineralization. Collectively, these results suggest that trifol may serve as an effective phytomedicine for bone diseases such as osteoporosis.


Uncovering the universality of self-replication in protein aggregation and its link to disease.
Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-growth mechanism, from those associated with disease, over those whose aggregates fulfill functional roles in biology, to those that aggregate only under artificial conditions. We find that, essentially, all such systems, regardless of their biological role, are capable of self-replication. However, for aggregates that have evolved to fulfill a structural role, the rate of self-replication is too low to be significant on the biologically relevant time scale. By contrast, all disease-related proteins are able to self-replicate quickly compared to the time scale of the associated disease. Our findings establish the ubiquity of self-replication and point to its potential importance across aggregation-related disorders.


Acute response to methylphenidate as a predictor of outcome of treatment with TCAs in the elderly.
Acute response to a single-dose, nonblind administration of methylphenidate 20 mg predicted outcome of treatment with desipramine in 42 elderly depressed inpatients. Treatment outcome was not predicted by the methylphenidate challenge in 29 patients who received amitriptyline. These findings are consistent with Maas' biogenic amine hypothesis and are encouraging with respect to the clinical utility of the methylphenidate challenge in geriatric depression.


[Expression of SSB gene in rats with early isehemic myocardium and its implications].
To examine the expression of Sjögren's syndrome antigen B (SSB) gene in rats with early ischemic myocardium. Adult healthy Sprague-Dawley rats were randomly divided into four groups (ischemia (MI), non-ischemia (NI), sham-operated (SO) and normal control (NO) groups). The expression of SSB and beta-actin gene in the myocardium was examined by real time PCR at 0 min, 5 min, 15 min, 30 min, 60 min, 120 min after ligation of the left anterior descending coronary artery (LAD). The expression of SSB gene was down-regulated after ischemia. Significantly lower expression of the gene in the rats with myocardial ischemia was found at 120 min after ligation compared with those before ligation and the control group at 120 min after ligation (P < 0.05 ). However, no significant differences were found between other groups (P > 0.05). SSB gene may be involved in the pathophysiologic regulating process in myocardial cells at the early stage of myocardial ischemia in rats.


Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy.
We tested patients with progressive supranuclear palsy and control subjects on a task of visuopatial attention. Targets preceded by cues on the same side were termed validly cued; and those on the opposite side, invalidly cued. For all subjects, validly cued targets were responded to faster than those that were invalidly cued. The difference between reaction times for invalidly and validly cued targets, which is hypothesized to measure attentional movement, was significantly increased for the patients. The performance of the controls on certain neuropsychological tests was correlated with their attentional ability. These correlations were altered by progressive supranuclear palsy. Physostigmine treatment of the patients induced a speeding of responses to invalidly cued targets as a function of the duration of the disease. These studies show defects in cognition and attention in patients with progressive supranuclear palsy and demonstrate that physostigmine reduces some of the abnormal visual attentional performance.


Development of Simple QSPR Models for the Prediction of the Heat of Decomposition of Organic Peroxides.
Quantitative structure-property relationships represent alternative method to experiments to access the estimation of physico-chemical properties of chemicals for screening purpose at R&D level but also to gather missing data in regulatory context. In particular, such predictions were encouraged by the REACH regulation for the collection of data, provided that they are developed respecting the rigorous principles of validation proposed by OECD. In this context, a series of organic peroxides, unstable chemicals which can easily decompose and may lead to explosion, were investigated to develop simple QSPR models that can be used in a regulatory framework. Only constitutional and topological descriptors were employed to achieve QSPR models predicting the heat of decomposition, which could be used without any time consuming preliminary structure calculations at quantum chemical level. To validate the models, the original experimental dataset was divided into a training and a validation set according to two methods of partitioning, one based on the property value and the other based on the structure of the molecules by the mean of PCA. Four QSPR models were developed upon the type of descriptors and the methods of partitioning. The 2 models issuing from the PCA based method were highlighted as they presented good predictive power and they are easier to apply than our previous quantum chemical based model, since they do not need any preliminary calculations.


Ten-year trajectories of stressors and resources at work: Cumulative and chronic effects on health and well-being.
Employing 5 waves of measurement over a period of 10 years, we explored the effects of exposure to constellations of conditions at work on physical and psychological strain, estimating the history of exposure over time. Specifically, we first tested if the 4 constellations postulated by the job demand-control (JDC) model, extended to include social stressors, could be identified empirically over time through a person-centered analysis. Second, we tested 2 specific effects of the history of exposure on physical and psychological strain: cumulative effects (i.e., history of exposure predicting strain) and chronic effects (i.e., history of exposure being associated with reduced reversibility in strain). Data were collected from 483 respondents who were at the end of their vocational training. The results supported the hypotheses, in that not all JDC constellations could be empirically identified, the majority of participants was in rather favorable constellations, and the differences between constellations, in terms of levels of demands and control, were more subtle than suggested by theoretically predefined constellations. Because the linear and quadratic solutions were largely comparable, we decided to adopt the linear ones. The expected cumulative and chronic effects were mostly confirmed: Unfavorable JDC constellations were associated with poorer health and well-being than favorable ones, when controlling for the initial level of the respective outcome variable, demographic variables, and for cumulative private stressors (cumulative effects). These differences largely remained after further adjustments for current conditions at work (chronic effects). (PsycINFO Database Record


[Migrant workers in agriculture and animal husbandry: experiences of health surveillance].
In Italy, 5 millions migrants live and work. Among them, the employment rate is much higher in comparison with the Italians' one (75% versus 62%). The well known "healthy migrant effect" is confirmed by statistics from the National Institute for Statistics: according to it, migrants access the National Health System for pregnancy and delivery and for accidents. The chronic pathology is not a major concern. Moreover, their work ability is generally complete, without any limitation. Nevertheless, migrants seem to represent a vulnerable subgroup with regard to the risk of 1) occupational injuries: this is strongly linked with the risk of Tetanus infection; 2) disorders of the metabolism, like hyperglycaemia and hyperlipemia, which is linked to a higher cardiovascular risk. In this light data from health surveillance carried out by the International centre for Rural Health of the San Paolo University Hospital in agricultural setting in the Region of Lombardy and the participation of the Centre itself to the Promovax EC-cofunded project are presented.


Long-term hypokalemia in acute myeloid leukemia.
A 48-year-old man suffering from acute myeloid leukemia presented a hypokalemia that persisted almost constantly during 18 months despite total hematological remission. The renal investigation demonstrated a hypokalemic nephropathy with an impairment of urinary concentrating function. Light and electron microscopy showed renal lesions related to potassium depletion. We did not observe specific lesions explaining the renal potassium wasting. Metabolic studies showed persistent hyperkaluresis, which appeared to be the main kaliopenic factor. We also found hypomagnesemia and changes of the renin-aldosterone system. We observed a hyperreninism, probably due to hypokalemia and a slight hyperaldosteronism, which could have been one of the kaluretic agents.


Pregnancy-induced haemophagocytic lymphohistiocytosis.
Haemophagocytic lymphohistiocytosis is an aggressive and life-threatening syndrome of excessive immune activation. It is associated with various aetiologies, including infections, collagen vascular diseases and malignancies. Pregnancy-induced immune dysregulation in genetically susceptible women may also play a critical role in haemophagocytic lymphohistiocytosis. Our case involves that of a 23-year-old pregnant woman who presented at 22 weeks gestation with tachycardia, swinging pyrexia, rigors and generalised myalgia. Refractory hypotension to intravenous fluids and rise in lactate level required admission to the intensive care unit for vasopressor support. Despite treatment with broad-spectrum antibiotics for presumed sepsis, she made little clinical improvement. Investigations for infection and rheumatological disease were unremarkable. A pronounced hyperferritinaemia, hypertriglyceridaemia and cytopenia raised the suspicion of haemophagocytic lymphohistiocytosis. Subsequent elevated CD25 levels helped establish the diagnosis. Treatment with corticosteroids and intravenous immunoglobulin provided a transient response in regard to temperature control and cardiovascular stability. The decision was made to treat her with anakinra, an interleukin-1 receptor antagonist. She responded well to this with a complete resolution of her symptoms and normalisation of her ferritin levels over the course of some weeks. Because of progressive slowing of foetal growth and abnormal umbilical artery Dopplers and cardiotocography, she eventually had an emergency caesarean section at 31 + 5 weeks. There were no foetal abnormalities.


Structure and expression of the SNF1 gene of Saccharomyces cerevisiae.
The SNF1 gene of Saccharomyces cerevisiae is essential for normal regulation of gene expression by glucose repression. A functional SNF1 gene product is required to derepress many glucose-repressible genes in response to conditions of low external glucose. In the case of the SUC2 structural gene for invertase, SNF1 acts at the RNA level. We have reported the isolation of a cloned gene that complements the snf1 defect in S. cerevisiae and that is homologous to DNA at the SNF1 locus (J. L. Celenza and M. Carlson, Mol. Cell. Biol. 4:49-53, 1984). In this work we identified a 2.4-kilobase polyadenylate-containing RNA encoded by the SNF1 gene and showed that its level is neither regulated by glucose repression nor dependent on a functional SNF1 product. The position of the SNF1 RNA relative to the cloned DNA was mapped, and the direction of transcription was determined. The cloned DNA was used to disrupt the SNF1 gene at its chromosomal locus. Gene disruption resulted in A Snf1- phenotype, thereby proving that the cloned gene is the SNF1 gene and showing that the phenotype of a true null mutation is indistinguishable from that of previously isolated snf1 mutations.


Evidence for more than one mechanism of plasmid-determined tetracycline resistance in Escherichia coli.
The basis of tetracycline resistance mediated by TetA determinants and joint resistance to tetracycline and minocycline coded by TetB determinants was investigated. The TetA class of determinants was represented by those carried on plasmids pSC101, RP1 and pIP7 and TetB by Tn10. The relationships between expression of tetracycline and minocycline resistance and accumulation of these antibiotics suggest that there are three mechanisms of plasmid-determined resistance conferring (1) about a 10- to 20-fold increase in resistance to tetracycline that is not associated with decreased antibiotic accumulation, (2) a 4- to 7-fold increase in resistance to tetracycline that is associated with decreased drug accumulation, and (3) about a 2- to 3-fold increase in resistance to both tetracycline and minocycline that is not associated with decreased accumulation of either antibiotic. Mechanism 1 was coded by the tetracycline resistance determinant of pSC101 (TetA), mechanisms 1 and 2 by the determinants in RP1 and pIP7 (TetA) and all three mechanisms by Tn10 (TetB).


Expression and localization of bestrophin during normal mouse development.
Best macular dystrophy is caused by mutations in the VMD2 gene, which encodes the protein bestrophin. The purpose of this study was to determine the postnatal onset of expression of bestrophin mRNA and protein in the mouse retinal pigment epithelium (RPE). Rabbit anti-mouse bestrophin polyclonal antisera designated Pab-003 was generated against a peptide derived from the C terminus of mouse bestrophin and characterized by Western blot and immunofluorescence staining of transfected cells. Expression of bestrophin mRNA during ocular development was studied with quantitative PCR. Bestrophin protein expression in the developing eye was observed by using immunohistochemistry. The onset of mouse phototransduction was determined by conventional electroretinography (ERG). Bestrophin mRNA was detected at embryonic day 15 in whole mouse eyes by RT-PCR. Real-time quantification of mouse bestrophin mRNA levels indicated that the highest levels of mRNA were present in the early postnatal period. In contrast, bestrophin in the RPE was first detected at postnatal day (P)10 by immunohistochemistry. Phototransduction, as determined by the presence of an ERG a-wave, was first observed at P10. The results of this study show that mouse bestrophin mRNA is present in the eye during embryogenesis and significantly precedes the onset of bestrophin protein expression at P10. The appearance of bestrophin in the basolateral plasma membrane of the RPE is coincident with the first detectable ERG a-wave. Because bestrophin is thought to play a role in generating the light peak, a late response of the ERG, these data support a temporal role for bestrophin in RPE responses to light. Furthermore, bestrophin protein appears to be a very late marker of RPE differentiation and to be subject to strong translational control.


Joint learning of labels and distance metric.
Machine learning algorithms frequently suffer from the insufficiency of training data and the usage of inappropriate distance metric. In this paper, we propose a joint learning of labels and distance metric (JLLDM) approach, which is able to simultaneously address the two difficulties. In comparison with the existing semi-supervised learning and distance metric learning methods that focus only on label prediction or distance metric construction, the JLLDM algorithm optimizes the labels of unlabeled samples and a Mahalanobis distance metric in a unified scheme. The advantage of JLLDM is multifold: 1) the problem of training data insufficiency can be tackled; 2) a good distance metric can be constructed with only very few training samples; and 3) no radius parameter is needed since the algorithm automatically determines the scale of the metric. Extensive experiments are conducted to compare the JLLDM approach with different semi-supervised learning and distance metric learning methods, and empirical results demonstrate its effectiveness.


Students' preferred teaching techniques for biochemistry in biomedicine and medicine courses.
The aim of this study was to investigate the students' preferred teaching techniques, such as traditional blackboard, power-point, or slide-projection, for biochemistry discipline in biomedicine and medicine courses from São Paulo State University, UNESP, Botucatu, São Paulo, Brazil. Preferences for specific topic and teaching techniques were determined from questionnaires on a Liquert scale from 1 to 5 (strongly disagree; disagree; neither agree, nor disagree; agree; strongly agree) distributed at the end of biochemistry discipline to 180 biomedical students (30 students/year) and 540 medical students (90 students/year), during the years 2000-2005. Despite of the different number of hours applied to the course topics for the two groups of students, the majority of undergraduates from biomedicine and medicine preferred metabolic topics. Although the perception of a medical student is expected to be different than that of a biomedical student, as the aims of the two programs are different, 92.4% of students from each course agreed or strongly agreed with the biochemistry topics, and 92.1% thought highly on this subject. The majority of students, a number of 139 undergraduates from biomedicine and 419 from medicine course, preferred traditional blackboard teaching than slide-projection, or power-point class. In conclusion, it is imperative that the health courses reflect on sophisticated technology and data presentation with high density of information in biochemistry discipline. The traditional classes with blackboard presentation were most favored by students from biomedicine and medicine courses. The use of students' preferred teaching techniques might turn biochemistry more easily understood for biomedical and medical students.


Association between panic disorder and childhood adversities: a systematic review and meta-analysis.
Adverse childhood experiences (ACEs) increase the risk of mental health difficulties in general, but the link to panic disorder (PD) has received comparatively little attention. There are no data for the magnitudes between ACEs and PD. This systematic review and meta-analysis estimated the overall, as well as the subgroups, odds ratio of having PD in adults who report ACEs, compared to adults who do not. The study was pre-registered on PROSPERO [CRD42018111506] and the database was searched in June 2021. In order to overcome the violation of independent assumptions due to multiple estimations from the same samples, we utilized a robust variance estimation model that supports meta-analysis for clustered estimations. Accordingly, an advanced method relaxing the distributional and asymptotic assumptions was used to assess publication bias and sensitivity. The literature search and screening returned 34 final studies, comprising 192,182 participants. Ninety-six estimations of 20 types of ACEs were extracted. Pooled ORs are: overall 2.2, CI (1.82-2.58), sexual abuse 1.92, CI (1.37-2.46), physical abuse 1.71, CI (1.37-2.05), emotional abuse 1.61, CI (0.868-2.35), emotional neglect 1.53, CI (0.756-2.31), parental alcoholism 1.83, CI (1.24-2.43), and parental separation/loss 1.82, CI (1.14-2.50). No between-group difference was identified by either sociolegal classification (abuse, neglect, household dysfunction) or threat-deprivation dimensions (high on threat, high on deprivation and mixed). There are links of mild to medium strength between overall ACEs and PD as well as individual ACEs. The homogeneous effect sizes across ACEs either suggest the effects of ACEs on PD are comparable, or raised the question whether the categorical or dimensional approaches to classifying ACEs are the definitive ways to conceptualize the impact of ACEs on later mental health.


One-Year Outcomes of Acute Decompensated Systolic Heart Failure in Taiwan: Lessons from TSOC-HFrEF Registry.
Heart failure (HF) is a global health problem. The Taiwan Society of Cardiology-Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry was a multicenter, observational survey of patients admitted with HFrEF in Taiwan. The aim of this study was to report the one-year outcome in this large-cohort of hospitalized patients presenting with acute decompensated HFrEF. Patients hospitalized for acute HFrEF were recruited in 21 hospitals in Taiwan. A total of 1509 patients were enrolled into the registry by the end of October 2014. Clinical status, readmission rates and dispensed medications were collected and analyzed 1 year after patient index hospitalization. Our study indicated that re-hospitalization rates after HFrEF were 31.9% and 38.5% at 6 and 12 months after index hospitalization, respectively. Of these patients, 9.7% of them were readmitted more than once. At 6 and 12 months after hospital discharge, all-cause mortality rates were 9.5% and 15.9%, respectively, and cardiovascular mortality rates were 6.8% and 10.5%, respectively. Twenty-three patients (1.5%) underwent heart transplantation. During a follow-up period of 1 year, 46.4% of patients were free from mortality, HF re-hospitalization, left ventricular assist device use and heart transplantation. At the conclusion of follow-up, 57.5% of patients were prescribed either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers; also, 66.3% were prescribed with beta-blockers and 40.8% were prescribed with mineralocorticoid receptor antagonists. The TSOC-HFrEF registry showed evidence of suboptimal practice of guideline-directed medical therapy and high HF re-hospitalization rate in Taiwan. The one-year mortality rate of the TSOC-HFrEF registry remained high. Ultimately, our data indicated a need for further improvement in HF care.


Sleep deprivation and its associated factors among general ward patients at a tertiary care hospital in Pakistan.
To estimate the occurrence rate of sleep deprivation and to identify the environmental, staff-related and patient-related factors associated with SD among general ward patients of a tertiary care hospital in Pakistan. In a cross-sectional study, a pre-tested questionnaire was administered to 108 patients admitted into the general medical and general surgical wards of Aga Khan University Hospital, Karachi. In all, 50 (46.3%) respondents felt deprived of adequate sleep in the hospital. Worry about illness disturbed the night-time sleep of 47 (43.5%) patients; most of these had SD (70%) (p < 0.001). Other patients' noise disturbed 31.5% of study subjects and a significant majority (68%) of these had SD (p = 0.003). Over 17% of study subjects reported cell phone's ringing as a disturbing factor; more by those with SD (68%) compared to those with no SD (32%); again the difference was significant (p = 0.003). Physical discomfort and presence of cannula were reported as disturbing factors by 41.7% and 28.7% of the study subjects respectively but these were not significantly associated with SD. Our study revealed that sleep deprivation occurs commonly among general ward patients in tertiary care setting. Factors found to be associated with SD were amenable to modification to a greater extent.


Nitrile Infrared Intensities Characterize Electric Fields and Hydrogen Bonding in Protic, Aprotic, and Protein Environments.
Nitriles are widely used vibrational probes; however, the interpretation of their IR frequencies is complicated by hydrogen bonding (H-bonding) in protic environments. We report a new vibrational Stark effect (VSE) that correlates the electric field projected on the -C≡N bond to the transition dipole moment and, by extension, the nitrile peak area or integrated intensity. This linear VSE applies to both H-bonding and non-H-bonding interactions. It can therefore be generally applied to determine electric fields in all environments. Additionally, it allows for semiempirical extraction of the H-bonding contribution to the blueshift of the nitrile frequency. Nitriles were incorporated at H-bonding and non-H-bonding protein sites using amber suppression, and each nitrile variant was structurally characterized at high resolution. We exploited the combined information available from variations in frequency and integrated intensity and demonstrate that nitriles are a generally useful probe for electric fields.


Role of beta-lactamases in the resistance of gram-negative bacilli to beta-lactam antibiotics.
Few studies in animal models or humans have been performed to prove that the mechanism of resistance to beta-lactam antibiotics in the presence of beta-lactamases is similar in vivo and in vitro. In vivo, it seems likely that different parameters will influence each other: the penetration of the antibiotic into the site of infection; the stability of the drug; and the organism responsible for the infection, which affects the type and amount of beta-lactamase released into the environment. In vitro, the different enzymatic parameters responsible for the inactivation of various compounds have been well defined. However, overall resistance to beta-lactams in the presence of beta-lactamase may also be influenced by the function of the outer membrane in gram-negative bacteria.


Time-sensitive approach in the management of acute heart failure.
Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is 'time sensitive' and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the 'time-sensitive' approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.


Measuring body condition of lizards: a comparison between non-invasive dual-energy X-ray absorptiometry, chemical fat extraction and calculated indices.
Condition indices (CIs) are used in ecological studies as a way of measuring an individual animal's health and fitness. Noninvasive CIs are estimations of a relative score of fat content or rely on a ratio of body mass compared to some measure of size, usually a linear dimension such as tarsus or snout-vent length. CIs are generally validated invasively by lethal fat extraction as in a seasonal sample of individuals in a population. Many alternatives to lethal fat extraction are costly or time consuming. As an alternative, dual-energy X-ray absorptiometry (DXA) allows for non-destructive analysis of body composition and enables multiple measurements during an animal's life time. DXA has never been used for ecological studies in a small, free-ranging lizard before, therefore we calibrated this method against a chemical extraction of fat from a sample of 6 geckos (Israeli fan toed gecko Ptyodactylus guttatus) ranging in body mass between 4.2-11.5 g. We then used this calibrated DXA measurements to determine the best linear measurement calculated CI for this species. We found that fat mass measured with DXA was significantly correlated with the mass of chemically extracted fat for specimens more than 4.8 g (N = 5, R2 = 0.995, P < 0.001). Fat percentage regressed with body mass significantly predicted the DXA fat percentage (N = 29, R2adj. = 0.862, p < 0.001). Live wet mass was significantly correlated with predicted fat mass (N = 30, R2 = 0.984, P < 0.001) for specimens more than 4.8 g. Among the five calculated non-invasive CIs that we tested, the best was mass/SVL. We recommend that in situations where DXA cannot be used, that the most accurate of the body condition estimators for this species is mass/SVL (snout-vent length) for both sexes.


Tolvaptan can improve clinical course in responders.
We previously defined "responders" as patients with increases in urine volume (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that responders to TLV could be predicted with considerable accuracy by urine osmolality (U-OSM) levels. Responders and non-responders to TLV should be associated with different clinical courses after a certain time following TLV administration. Therefore, the aim of the present study was to validate our definition of responders by clinical parameters 1 week after administration of TLV. Data (n = 85) were obtained from in hospital patients with decompensated heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at 1 week after the administration of TLV were compared with those of baseline. Sixty patients (70.6%) were "responders", in whom UV on day 1 increased after the administration of TLV compared with day 0. "Non-responders" were older, and had higher serum creatinine concentration and lower baseline U-OSM than "responders". Serum creatinine concentration increased significantly in "non-responders", but was unchanged in "responders". Body weight, plasma B-type natriuretic peptide concentration, and HF symptom score decreased significantly in "responders", but remained unchanged in "non-responders". Increases in UV after the first administration of TLV were closely correlated with improvement of congestive HF after 1 week of TLV treatment, which verified our definition of "responders" to TLV.


[Professional selection and successful residency training in anesthesiology-resuscitation].
The professional carrier of 356 residents, the 1960-2007 graduates of the Saint Petersburg Medical Academy of Postgraduate Education, was studied to specify approaches to professional selection of anesthesiologists. Thirty (8.4%) graduates did not work as anesthesiologists at all. It should be noted that most (n = 24) of the 30 graduates had successfully completed the residency. The anesthetic activities were generally altered under the influence of factors that are not related to successful education, namely financial, social, familial, etc. In this connection, long-term forecasting underlying professional selection appears to be of doubtful feasibility. The selection made within the first year of training (a follow-up by teachers) is valid. However, it is impossible to consider each residency graduate to be a well-trained anesthesiologist. An intermediate decision to solve this problem is to establish the new nationally accepted order: a graduate may start his/her professional career only at a university clinic or other large hospital especially licensed for this purpose, by being supervised by senior colleagues. Permission for fully independent practice should be given not earlier than after 2-3-year work at the above mentioned clinics.


Poly(ethylene oxide) (PEO) and poly(vinyl pyrolidone) (PVP) induce different changes in the colloid stability of nanoparticles.
The phase behavior of model polymer-colloid mixtures is measured for solutions approaching the "protein limit", that is, when the radius of gyration of the polymer (R(g)) is greater than or approximately equal to the radius of the colloid (R). Cationic nanoparticles are mixed with poly(ethylene oxide) (PEO) or poly(vinyl pyrolidone) (PVP) at size ratios of R(g)/R = 0.7 and 1.8. The addition of PEO to stable nanoparticle dispersions leads to depletion flocculation in both deionized water and buffer solutions. The instability mechanism for the PVP-nanoparticle system depends on the suspension medium. In water, bridging occurs below the saturation adsorption of PVP, whereas depletion phase separation is evident at concentrations exceeding those necessary to saturate the particle surface. In acidic buffer, PVP addition results in depletion phase separation. The difference between bridging and depletion is distinguished by both visual appearances and rheological measurements. There is no trend (within error bars) in the polymer concentration required to induce instability with increasing R(g)/R in contrast with theoretical predictions. This is most likely due to adsorption of polymer onto the particle surface.


Occupational identity crisis of professionals dealing with difficult adolescents.
This study tests the hypothesis of vulnerability in health and social care professionals dealing with difficult adolescents. This vulnerability appears to be underpinned by an occupational identity crisis that seems to diminish the ability of these professionals to recognize the suffering of these adolescents. A questionnaire was developed and then distributed during a network day bringing together members of various institutions and bodies working with difficult adolescents. Ninety-three professionals responded. Occupational identity weaknesses were identified: inadequate basic training, experiences of solitude, feelings of powerlessness and exposure, inadequate personal and institutional resources. Actors involved express their need for inter-institutional and inter-sectoral network but find it uneasy to implement. Some changes can be recommended to reduce this occupational identity crisis: increased efforts towards continuing training, development of possibilities of reflection within institutions, and more structured partnerships and actions.


EGFR mutation-positive NSCLC: factors to consider when deciding first-line therapy.
Introduction: Advanced non-small-cell lung cancers with EGFR mutation belong to the models of solid tumors which revealed the concept of oncogene addiction. For that reason, first, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are the major anti-cancer drugs used in this indication. Translational research is currently focused on induced mechanisms of resistance and aims to define the best first therapeutic option and the best multiline strategy.Areas covered: EGFR TKIs, alone or in combination, i.e. anti-angiogenic drugs or chemotherapy, have demonstrated their ability to improve median PFS and OS in large randomized phase 3 trials. All these combinations, now available in first-line for EGFR mutated advanced NSLC, need to integrate multiple factors like patients characteristics (age, co-morbidities, eligibility to platinum-based chemotherapy), presence of brain metastasis at diagnosis, and type of EGFR mutation. This review has 2 aims: (1) to discuss the current knowledge of therapies available in non pre-treated EGFR-mutated NSCLC; (2) to propose the best therapeutic option according to multiple parameters, either clinical or biological.Expert commentary: In 2020, we can affirm that osimertinib the first choice for patients with EGFR-mutated NSCLC. However, this has to be balanced with patient characteristics, type of EGFR mutation and new therapeutic options.


Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys.
The mechanisms of recovery of manual dexterity after unilateral lesion of the sensorimotor cortex in adult primates remain a matter of debate. It has been proposed that the cortical zone adjacent to the lesion may take over part of the function of the damaged cortex. To investigate further this possibility, two adult (4-5 years old) macaque monkeys were trained to perform a natural precision-grip task to assess hand dexterity. Intracortical microstimulations (ICMS) were used to map the hand area in M1 on both hemispheres. Ibotenic acid was then injected intracortically to damage the representation in M1 of the preferred hand. Subsequent histological analysis indicated that the hand representation in M1 was indeed lesioned, but, due to a spread of ibotenic acid, the lesion encroached a significant extent of the hand representation in the primary somatosensory cortex. A few minutes after infusion of ibotenic acid, there was a complete loss of dexterity of the preferred hand, which lasted for 1-2 months. Later, a progressive functional recovery of the affected hand took place over a 3- to 4-month period, reaching a stable level corresponding to 30% of the pre-lesion behavioral score. ICMS remapping, conducted nine months after the lesion, revealed that stimulation of the intact or lesioned M1 did not induce any visible movement of the recovered hand. The M1 hand representation on the intact hemisphere was similar to that observed before the lesion. Transient inactivation of the M1 hand/arm areas or of the dorsal and ventral premotor cortical areas (PM) on both hemispheres was undertaken by using microinjections of the GABA-agonist muscimol. Inactivations of M1 had no effect. Inhibition of PM in the damaged hemisphere suppressed the recovered manual dexterity of the affected hand. These results suggest that PM plays a significant role in the incomplete functional recovery of hand dexterity following unilateral damage of the sensorimotor cortex in adult monkeys.


A stress-responsive caleosin-like protein, AtCLO4, acts as a negative regulator of ABA responses in Arabidopsis.
Caleosins or related sequences have been found in a wide range of higher plants. In Arabidopsis, seed-specific caleosins are viewed as oil-body (OB)-associated proteins that possess Ca(2+)-dependent peroxygenase activity and are involved in processes of lipid degradation. Recent experimental evidence suggests that one of the Arabidopsis non-seed caleosins, AtCLO3, is involved in controlling stomatal aperture during the drought response; the roles of the other caleosin-like proteins in Arabidopsis remain largely uncharacterized. We have demonstrated that a novel stress-responsive and OB-associated Ca(2+)-binding caleosin-like protein, AtCLO4, is expressed in non-seed tissues of Arabidopsis, including guard cells, and down-regulated following exposure to exogenous ABA and salt stress. At the seed germination stage, a loss-of-function mutant (atclo4) was hypersensitive to ABA, salt and mannitol stresses, whereas AtCLO4-overexpressing (Ox) lines were more hyposensitive to those stresses than the wild type. In adult stage, atclo4 mutant and AtCLO4-Ox plants showed enhanced and decreased drought tolerance, respectively. Following exposure to exogenous ABA, the expression of key ABA-dependent regulatory genes, such as ABF3 and ABF4, was up-regulated in the atclo4 mutant, while it was down-regulated in AtCLO4-Ox lines. Based on these results, we propose that the OB-associated Ca(2+)-binding AtCLO4 protein acts as a negative regulator of ABA responses in Arabidopsis.


Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults.
To investigate cross-sectional and longitudinal associations between serum leptin levels and knee cartilage thickness in older adults. A prospective cohort of 163 randomly selected subjects (mean 63 years, range 52-78, 46% women) was studied. Knee cartilage thickness at medial tibial, lateral tibial, femoral and patellar sites was determined using T1-weighted fat-suppressed MRI. Serum leptin levels were measured by radioimmunoassay. Radiographic osteoarthritis, body fat (%), trunk fat (%), weight and height were measured, and body mass index (BMI) was calculated. Cross-sectionally, serum levels of leptin were negatively associated with femoral (β: -0.013, 95% CI -0.022 to -0.003), medial tibial (β: -0.009, 95% CI -0.018 to -0.001), lateral tibial (β: -0.012, 95% CI -0.021 to -0.003) and patellar (β: -0.014, 95% CI -0.026 to -0.002) cartilage thickness after adjustment for covariates. Moreover, BMI, trunk fat and total body fat were negatively associated with cartilage thickness, and the significant associations disappeared after further adjustment for leptin. Longitudinally, both baseline leptin and change in leptin were associated with greater changes in medial tibial cartilage thickness (β: -0.004, 95% CI -0.007 to -0.001 and β: -0.009, 95% CI -0.018 to -0.001, respectively) in multivariable analyses. Serum levels of leptin are independently and consistently associated with reduced cartilage thickness cross-sectionally and longitudinally. In addition, the associations between adiposity measures and cartilage thickness are mediated by leptin, suggesting leptin may play a key role in cartilage thinning.


Epigenetic histone modulations of PPARγ and related pathways contribute to olanzapine-induced metabolic disorders.
The antipsychotic drug olanzapine is widely used in the treatment of schizophrenia, bipolar and other mental disorders; however, it causes serious metabolic disorders, including dyslipidemia. Our previous studies have identified that olanzapine activated expression of the sterol regulatory element binding transcription factor 1 (SREBP-1) gene, a key transcriptional factor for lipogenesis in the liver and adipocytes. SREBP-1 has been reported to positively regulate the peroxisome proliferator-activated receptor gamma (PPARγ), a master regulator in the process of adipogenesis. This study aimed to investigate epigenetic modulations of the hepatic PPARγ pathway in olanzapine-induced lipid dysfunctions. Olanzapine led to significant increases of body weight gain, white adipose tissue, fasting triglyceride, and fat accumulation in the liver. A significant upregulation of PPARγ was observed in olanzapine-treated rats. ChIP-deep sequencing showed the increase of H3K4me2 binding on the whole gene loci of key regulators of adipogenesis and lipogenesis, the Pparg, Srebp-1, Cebps families (Cebpa, Cebpb and Cebpd), the Signal transducer and activator of transcription 5 families (Stat5a and Stat5b) and Klfs families (Klf9 and Klf15), as well as muscarinic M3 receptor (Chrm3). ChIP-qPCR revealed that H3K9me3 binding on the promoter of Pparg2 was significantly decreased. Consistently, KDM4B, KDM1A and PHF2, the three histone demethylases responsible for site-specific erasure of H3K9me, was increased in olanzapine-treated rats. These results suggested that olanzapine acted as stimuli to trigger the cascade of adipogenesis and lipogenesis through modulating hepatic histone modifications and subsequently upregulating key transcriptional factors. These findings provided new insight into effective strategies for the prevention and treatment of metabolic side-effects induced by antipsychotic medication.


Formation of bone-like mineralized matrix by periodontal ligament cells in vivo: a morphological study in rats.
Periodontal ligament (PDL) is a unique connective tissue that not only connects cementum and alveolar bone to support teeth, but also plays an important role in reconstructing periodontal tissues. Previous studies have suggested that PDL cells have osteogenic potential; however, they lack precise histological examinations. Here, we studied bone-like matrix formation by PDL cells in rats using morphological techniques. Rat and human PDL cells exhibited substantial alkaline phosphatase activity and induced mineralization in vitro. RT-PCR analyses showed that PDL cells expressed the osteoblast markers, Runx2, osterix, and osteocalcin. These results suggest that PDL cells share similar phenotypes with osteoblasts. To examine the bone-like matrix formation in vivo, PDL cells isolated from green fluorescent protein (GFP)-transgenic rats were inoculated with hydroxyapatite (HA) disks into wild-type rats. Five weeks after the implantation, the pores in HA disks were occupied by GFP-positive cells. Mineralized matrix formation was also found on the surface of HA pores. At 12 weeks, some of the pores were filled with bone-like mineralized matrices (BLMM), which were positive for the bone matrix proteins, osteopontin, bone sialoprotein, and osteocalcin. Immunohistochemical examination revealed that most of the osteoblast- and osteocyte-like cells on or in the BLMM were GFP-positive, suggesting that the BLMM were directly formed by the inoculated PDL cells. On the pore surfaces, Sharpey's fiber-like structures embedded in cementum-like mineralized layers were also observed. These results collectively suggest that PDL cells have the ability to form periodontal tissues and could be a useful source for regenerative therapies of periodontal diseases.


Can mass media interventions reduce child mortality?
Many people recognise that mass media is important in promoting public health but there have been few attempts to measure how important. An ongoing trial in Burkina Faso (ClinicalTrials.gov, NCT01517230) is an attempt to bring together the very different worlds of mass media and epidemiology: to measure rigorously, using a cluster-randomised design, how many lives mass media can save in a low-income country, and at what cost. Application of the Lives Saved Tool predicts that saturation-based media campaigns could reduce child mortality by 10-20%, at a cost per disability-adjusted life-year that is as low as any existing health intervention. In this Viewpoint we explain the scientific reasoning behind the trial, while stressing the importance of the media methodology used.


The early electroclinical manifestations of infantile spasms: A video EEG study.
Infantile spasms are described as flexor extensor and mixed; but more features of their semiology and ictal electroencephalography (EEG) changes are sparse in the literature. The purpose of the study was to describe the clinical and ictal video-EEG characteristics of consecutive cases with infantile spasms and to try to find an association with the etiology. The clinical phenomenology and EEG characteristics on video-EEG were analyzed in 16 babies with infantile spasms. A total of 869 spasms were reviewed. Nine (56.3%) showed focal seizures at least once during the recording and 1 (6.3%) had multifocal myoclonus in addition to the spasms. The duration of the cluster and interval between spasms was totally variable in all patients. Lateralizing phenomena were present in at least some of the spasms in all patients. Unilateral manual automatism in the form of holding the pinna was noted in three patients following the spasm. The ictal EEG activity in the majority (75%) was the slow wave. Four (25%) showed fast generalized spindle-like ictal discharges. Spikes, spike and wave activity, or electrodecremental pattern alone during the ictus was seen in none. On bivariate analysis, no factor noted on the video EEG had association with the etiology. Infantile spasms could be associated with focal and other seizures, has unique, non-uniform and variable semiology from patient to patient. The ictal EEG manifestation in the majority (75%) of our patients was the slow wave transient with 25% showing generalized fast spindle-like activity.


Receptor Activity-modifying Proteins 2 and 3 Generate Adrenomedullin Receptor Subtypes with Distinct Molecular Properties.
Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins 2 and 3 (RAMP2 and RAMP3), respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMP2 and -3 on the activation and conformation of the CLR subunit of AM receptors, we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors, and determined the effects on cAMP signaling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modeling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function.


Published estimates of group differences in multisensory integration are inflated.
A common measure of multisensory integration is the McGurk effect, an illusion in which incongruent auditory and visual speech are integrated to produce an entirely different percept. Published studies report that participants who differ in age, gender, culture, native language, or traits related to neurological or psychiatric disorders also differ in their susceptibility to the McGurk effect. These group-level differences are used as evidence for fundamental alterations in sensory processing between populations. Using empirical data and statistical simulations tested under a range of conditions, we show that published estimates of group differences in the McGurk effect are inflated when only statistically significant (p < 0.05) results are published. With a sample size typical of published studies, a group difference of 10% would be reported as 31%. As a consequence of this inflation, follow-up studies often fail to replicate published reports of large between-group differences. Inaccurate estimates of effect sizes and replication failures are especially problematic in studies of clinical populations involving expensive and time-consuming interventions, such as training paradigms to improve sensory processing. Reducing effect size inflation and increasing replicability requires increasing the number of participants by an order of magnitude compared with current practice.


Flavihumibacter solisilvae sp. nov., isolated from forest soil.
A Gram-stain-positive, strictly aerobic, yellow colony-forming bacterium, designated strain 3-3(T), was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods without gliding motility, showing oxidase- and catalase-positive reactions. Growth was observed at 20-37 °C (optimum, 28 °C) and pH 5.5-9.5 (optimum, pH 7.5). The major cellular fatty acids were iso-C(15 : 0), iso-C(15 : 1) G and summed feature 3 (comprising C(16 : 1)ω6c and/or C(16 : 1)ω7c). Strain 3-3(T) contained phosphatidylethanoamine, three unidentified aminolipids and three unidentified lipids. The G+C content of the genomic DNA was 49.5 mol% and the only isoprenoid quinone detected was menaquinone 7 (MK-7). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 3-3(T) formed a tight phylogenetic lineage with Flavihumibacter petaseus T41(T) with a bootstrap value of 100%. Strain 3-3(T) was related most closely to F. petaseus T41(T) with 97.3% 16S rRNA gene sequence similarity and the level of DNA-DNA relatedness between the two was 9.4±1.2%. Based on phenotypic, chemotaxonomic and molecular features, strain 3-3(T) represents a novel species of the genus Flavihumibacter, for which the name Flavihumibacter solisilvae sp. nov. is proposed. The type strain is 3-3(T) ( = KACC 17917(T) = JCM 19891(T)).


Behavioral effects of children's nearpoint lenses.
Procedures in clinical optometry include the therapeutic and preventive use of lenses for the express purpose of favorably modifying visual behavior in nearpoint activities, especially for children. The research bases for such procedures have been greatly elaborated in recent years. Research evidence now exists to clarify some of the actual effects of lenses upon behavior, indicating possible ways of explaining the underlying mechanisms or processes of such effects, while further suggesting clinical techniques for the appropriate diagnostic determination of nearpoint lens prescriptions.


Development of high-density single-mode polymer waveguides with low crosstalk for chip-to-chip optical interconnection.
High-density single-mode polymer waveguides were fabricated for chip-to-chip optical interconnection. The waveguides were designed as minimized mode field diameters for the lowest inter-channel crosstalk caused by mode coupling. The optimum relative index difference chosen was 1.2% to ensure compatibility with low crosstalk and wide fabrication tolerances. The 60-mm-length linear waveguides demonstrated a low propagation loss of 0.6 dB/cm and -45 dB crosstalk at 1310 nm. Also, a new crosstalk mechanism for a curved waveguide was revealed.


Characteristics of corneal ectasia after LASIK for myopia.
There are numerous reports of corneal ectasia after laser in situ keratomileusis (LASIK) for myopia without a consistent definition of this condition or a definitive etiology. We conducted a retrospective analysis of published case reports to describe common characteristics of this postoperative event and compared them with findings from a group of successful LASIK patients. A MEDLINE search for "LASIK" and "ectasia" yielded 21 relevant articles published before May 2003 (n = 86 eyes, 59 patients). A comparison group (n = 103 eyes, 63 patients) was selected from a clinic-based sample of successful LASIK patients with 12 months of follow-up after treatment. Descriptive statistics are reported as median and interquartile range. Comparisons were performed using the Wilcoxon rank sum, Wilcoxon signed rank, and chi-square tests. Time to diagnosis of ectasia after LASIK was 13 months (6 to 20 months). Residual myopia in the ectasia group was -3.69 D (-6.00 to -2.13 D) and was significantly greater than the comparison group, -0.38 D (-0.75 to 0.00 D), P < 0.001. After surgery, eyes with ectasia had increased corneal toricity 2.87 D (2.00 to 4.9 D) with increased oblique astigmatism 1.3 D (0.23 to 2.89 D) relative to eyes in the comparison group 0.00 D (0.00 to 0.08 D), and a loss of 2 lines (-0.5 to -6 lines) of best spectacle-corrected visual acuity (all P < 0.001). Thirty-five percent of reported cases resulted in subsequent corneal transplantation. Preoperative characteristics of corneal ectasia include worse visual acuity, less corneal thickness, greater residual myopia, and greater corneal toricity than nonectatic eyes. Treatment factors associated with corneal ectasia after LASIK are greater stromal ablation and less residual stromal bed thickness. Postoperative characteristics of corneal ectasia are myopic refractive error with increased astigmatism, worse spectacle-corrected visual acuity, increased corneal toricity with topographic abnormality, and progressive corneal thinning.


Is Hematopoietic Clonality of Indetermined Potential a Risk Factor for Pulmonary Embolism?
Background Unprovoked pulmonary embolism (uPE) is a severe and frequent condition. Identification of new risk factors is mandatory to identify patients that would benefit from a long-term treatment. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations that drive clonal expansion in the absence of cytopenia. Its prevalence is estimated of 5% in the population above 65 years. Since inflammation and endothelial dysfunction may share a pathophysiological pathway(1), we hypothesized that CHIP, may be a risk factor for uPE. Methods We conducted a pilot retrospective observational study. Patients with iPE between 18 to 65 years old were included. PE was considered as unprovoked, when no transient nor persistant risk factor was present and when thrombophilia testing was negative. We excluded documented atherosclerosis, personal or familial history of VTE and presence of cytopenias. CHIP proportion in uPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53 . Results Upon 61 patients with uPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20%) IC95% [10 - 20]. 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2 . There was no diference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers. Conclusion We report for the first time, the presence of high rates of CHIP in patients presenting with uPE. Thus, CHIP may be a new risk factor for VTE. These results need to be confirmed in an ongoing prospective case-control study including more patients and using a more diverse gene panel to better determine CHIP incidence in uPE.


In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy.
In vivo measurement of retinal blood flow is obtained by measuring the blood velocity of erythrocytes and lumen diameters of the blood vessels using an adaptive optics scanning laser ophthalmoscope. Erythrocyte velocity is measured by tracking erythrocytes moving across a horizontal scanning line. This approach provides high temporal bandwidth measurements, allowing the fluctuation of blood flow during cardiac cycles to be measured. The technique is most applicable to medium-sized blood vessels.


Multiple sclerosis as a comorbidity: a study of resource utilization and outcomes of care.
The purpose of this paper is to compare the resource utilization and outcomes of care of elderly hospitalized patients with multiple sclerosis (MS) as a comorbidity to a comparison group without multiple sclerosis, matched by age, gender, and diagnosis related group (DRG) using the 1989 Quality Care (QC) MEDPAR file. The results of this paper demonstrate some differences in resource use. MS discharges incur lower average charges ($8698 for MS discharges, $8977 for controls), although the results are not statistically significant. Proportionately fewer MS discharges use intensive or coronary care services (14.7% versus 18.5%, P < .05). MS patients had a lower, but not statistically significant, 30-day mortality rate than the comparison group matched by age, sex, and DRG (7.6% versus 8.8%), a lower rate of readmission (13.9% versus 16.7%, P < .05), and a lower rate of complications (2.6% versus 4.7%, P < .05), although the results are not consistent across DRGs. Charges, length of stay, and intensive/coronary care utilization were lower, as expected, for a subset of less comorbid MS discharges and controls with, at most, four diagnoses. In this subset, MS discharges and controls were not statistically different, with the exception of overall complication rates (1.0% for MS versus 4.1% for controls, P < .05) and surgical complication rates (2.1% for MS versus 10.0% for controls, P < .05). It is unclear whether these results are due to differences in disease severity, case-mix within DRG, surgical risk, patient surveillance, or quality of care.


The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm.
Human mitochondrial DNA (mtDNA) encodes 13 polypeptides of the electron transfer chain. Its replication is dependent on the nuclear-encoded polymerase gamma (POLG) and mitochondrial transcription factor A (TFAM). For POLG, only the polyglutamine tract, characterized by a series of CAG repeats, has been investigated in human sperm. However, TFAM is associated with the reduction in mtDNA content of testicular sperm. We have determined whether POLG and TFAM have functional roles in post-ejaculatory sperm mtDNA. Sperm samples were categorized as: normals, samples with one or two abnormal sperm parameters and oligoasthenoteratozoospermics (OATs). These were analysed by fluorescent PCR to determine the number of CAG repeats, real-time PCR for mtDNA copy number and immunocytochemistry and western blotting for patterns of expression for POLG, TFAM and the mtDNA-encoded COXI. Only the OAT group presented with a significantly higher incidence of heterozygosity for CAG repeats, higher mtDNA content and a lower percentage of sperm expressing POLG and TFAM. Paradoxically, good-quality sperm had fewer mtDNA copies but significantly more sperm expressed POLG, TFAM and COXI. Our data support the original findings that an association between sperm quality and POLG CAG repeats does exist. However, the biological significance of these variants in male infertility remains unclear, as these do not seem to affect mtDNA maintenance. The reduction in mtDNA content in normal samples likely reflects normal spermiogenesis, whereas increases in POLG and TFAM expression possibly compensate for the low mtDNA content, maintaining mitochondrial homeostasis.


Strengthening the Electrodes for Li-Ion Batteries with a Porous Adhesive Interlayer through Dry-Spraying Manufacturing.
The manufacturing technologies for electrodes have a great influence on the performance of Li-ion batteries. Manufacturing procedures largely determine the microstructure of electrodes, and thus affect how active materials are involved in the electrochemical reactions. However, the usage of solvent in the dominant slurry-casting method weakens its competence on obtaining desired microstructures and properties. In this study, an improved adhesion strength is achieved during the fabricaion of graphite anodes with our solvent-free manufacturing method. Through dry-spraying an interfacial "adhesion enhancer" layer between the current collector and the electrode coating, the mechanical strength (from 0.5 kPa to over 83.0 kPa) and electrochemical performance (from 24.2% to 92.4% as the capacity retention in 100 cycles) are significantly improved. Results here demonstrate a simple and economical route to practically control the microstructure of electrodes during manufacturing and potentiate the strategy enabled by dry-spraying to design and manufacture advanced batteries.


Two conserved histidine residues are critical to the function of the TagF-like family of enzymes.
The TagF protein from Bacillus subtilis 168 is the poly(glycerol phosphate) polymerase responsible for the synthesis of wall teichoic acid and is the prototype member of a poorly understood family of similar teichoic acid synthetic enzymes. Here we describe in vitro and in vivo characterization of TagF, which localizes the active site to the carboxyl terminus of the protein and identifies residues that are critical for catalysis. We also establish the first mechanistic link among TagF and similar proteins by demonstrating that the identified residues are also critical in the function of TagB, a homologous enzyme implicated as the glycerophosphotransferase responsible for priming poly(glycerol phosphate) synthesis. We investigated the dependence of TagF activity on pH and showed that deprotonation of a residue with a pK(a) near neutral is critical for proper function. Alteration of histidine residues 474 and 612 by site-directed mutagenesis abolished TagF activity in vitro (5000-fold reduction in k(cat)/K(m)) while variants in four other conserved acidic residues showed minimal loss of activity. Complementation using H474A and H612A mutant alleles failed to suppress a lethal temperature-sensitive tagF defect in vivo despite confirmation of robust expression by Western blot. When corresponding mutations were made to the homologous tagB gene, these alleles were unable to suppress a tagB temperature-sensitive lethal phenotype. These results extend the mechanistic observations for TagF across a wider family of enzymes and provide the first biochemical evidence for the relatedness of these two enzymes.


Use of ferrocenyl surfactants of varying chain lengths to study electron transfer reactions in native montmorillonite clay.
A series of ferrocenyl surfactants was tested as model compounds to study electron transfer reactions involving structural Fe(III) in clay minerals. The surfactants contain trimethylammonium headgroups, ferrocene tail groups, and intervening hydrocarbon chain lengths of one, six, or 11 carbons. Two factors considered to be decisive for electron transfer were addressed: (1) physical access of the surfactant ferrocene to the reactive sites through hexagonal holes in the clay lattice by X-ray diffraction (XRD) and small-angle X-ray scattering (SAXS) and (2) thermodynamic favorability of the overall oxidation/reduction reaction based on experimentally determined oxidation/reduction potentials. In suspensions of clay with the longer chain surfactants, (ferrocenylhexyl)trimethylammonim (FHTMA+) and (ferrocenylundecyl)trimethylammonium (FUTMA+), where electron transfer may be expected to be favored by both factors, physical accessibility, and thermodynamic favorability, ferroecene oxidation was observed by diffuse reflectance infrared spectroscopy (DRIFT), ultraviolet-visible spectroscopy (UV-vis), and visual color changes. In contrast, the shorter chain length surfactant, (ferrocenylmethyl)trimethylammonium (FMTMA+), did not participate in electron transfer with the clay, as substantiated by UV-vis and no visible color changes. Rigid conformation and/or higher oxidation/reduction potential than clay Fe can accountforthe lack of reaction. The utility and limitations of using these surfactants as model compounds is discussed.


PET/CT Assessment of Response to Therapy: Tumor Change Measurement, Truth Data, and Error.
We describe methods and issues that are relevant to the measurement of change in tumor uptake of (18)F-fluorodeoxyglucose (FDG) or other radiotracers, as measured from positron emission tomography/computed tomography (PET/CT) images, and how this would relate to the establishment of PET/CT tumor imaging as a biomarker of patient response to therapy. The primary focus is on the uptake of FDG by lung tumors, but the approach can be applied to diseases other than lung cancer and to tracers other than FDG. The first issue addressed is the sources of bias and variance in the measurement of tumor uptake of FDG, and where there are still gaps in our knowledge. These are discussed in the context of measurement variation and how these would relate to the early detection of response to therapy. Some of the research efforts currently underway to identify the magnitude of some of these sources of error are described. In addition, we describe resources for these investigations that are being made available through the Reference Image Database for the Evaluation of Response project. Measures derived from PET image data that might be predictive of patient response as well as the additional issues that each of these metrics may encounter are described briefly. The relationship between individual patient response to therapy and utility for multicenter trials is discussed. We conclude with a discussion of moving from assessing measurement variation to the steps necessary to establish the efficacy of PET/CT imaging as a biomarker for response.


Normal-appearing white matter structural integrity in incidentally discovered low-grade gliomas: a single institution study.
Incidentally discovered low-grade gliomas (iLGGs) are poorly reported in the literature and little is still known about their effects on white-matter structure. In this study, we investigated whether iLLG growth in either hemisphere could affect main white-matter association tracts and cortico-spinal tract. We retrospectively analyzed white-matter integrity in a group of 18 patients with iLGG having a mostly preserved cognitive status [1]. We identified two groups of patients, 13 having iLGG in left hemisphere (LH) and five in right hemisphere (RH) and maximum lesion overlap in inferior frontal gyrus and in medial frontal areas, respectively. A group of healthy controls (N.=20) was included. We carried out a univariate analysis of variance to inspect potential effect of interaction between hemisphere harboring the lesion (i.e., LH or RH) and hemisphere taken into account on number of streamlines and fractional anisotropy (FA) of reconstructed white-matter tracts. The sole significant interaction concerned left arcuate fasciculus, with patients with iLGG in LH having a lower number of streamlines than healthy controls; interaction involving FA was not significant for any of the fascicles. Lack of any other significant findings indicates overall preserved white matter. iLGG size and growth pattern could explain why white-matter status did not markedly differ with respect to the healthy controls. Findings therefore support evidence that iLGGs represent the earlier phase in natural history of LGGs and are discussed in a clinical perspective and in support to safe early surgery.


Progressive renal failure in surgically treated hyperparathyroidism.
Of 570 patients operated on for hyperparathyroidism, 18 subsequently died (between one day and 12 yr after operation). Pathological findings at necropsy in these patients have been reviewed. Four necropsies on patients with untreated hyperparathyroidism have also been reviewed for comparison. Of these 22 cases, 14 had renal failure at the time of death. This was attributed to the following: nephrocalcinosis 6; chronic glomerulonephritis 4; analgesic nephropathy 1; cystinuria 1; sarcoidosis 1; and polycystic disease 1. Of those with renal failure due to nephrocalcinosis, three had persistent hypercalcaemia after operation; the other three survived only for a short time. There was no evidence of residual nephrocalcinosis producing progressive renal failure if the plasma calcium concentration was corrected. In those with chronic glomerulonephritis, cystinuria, and polycystic disease, the hyperparathyroidism was considered to be tertiary to the renal disease but renal failure was not always present at the time of diagnosis.


Anti-inflammatory and side effects of cyclooxygenase inhibitors.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in inflammatory diseases, since they are effective in management of pain, fever, redness, edema arising as a consequence of inflammatory mediator release. Studies have shown that both therapeutic and side effects of NSAIDs are dependent on cyclooxygenase (COX) inhibition. COX isoforms have been named constitutive (COX-1) and inducible (COX-2). COX-1 catalyzes formation of cytoprotective prostaglandins in thrombocytes, vascular endothelium, stomach mucosa, kidneys, pancreas, Langerhans islets, seminal vesicles, and brain. Induction of COX-2 by various growth factors, proinflammatory agents, endotoxins, mitogens, and tumor agents indicates that this isoform may have a role in induction of pathological processes, such as inflammation. It is well known that therapy with COX inhibitors is associated with a number of side effects including gastrointestinal erosions, and renal and hepatic insufficiency. Such critical adverse reactions are mostly dependent on COX-1 inhibition. As a result of research focused on reduction of the adverse effects of NSAIDs, selective COX-2 inhibitors, such as celecoxib and rofecoxib have been developed. However, many data demonstrate that mechanisms of action of these drugs are multidirectional and complex. These drugs or their derivatives, which belong to the same group, have distinct pharmacological effects, side effects and potencies which implies that there may be more than two, five or even tens of COX isoforms.


Detection of activated platelets in urine by double immunofluorescence in children with IgA nephropathy.
The relationship between the activation of platelets (PLT) in urine and renal histological findings in children with IgA nephropathy (IgAN), thin basement membrane disease (TBMD), and minimal-change nephrotic syndrome (MCNS) was examined. The ratio of activated PLT to total PLT (activated and nonactivated PLT) was examined by double immunofluorescence using rhodamine-conjugated P selectin antibody (activated PLT) and fluorescein isothiocyanate conjugated PLT membrane glycoprotein antibody (GPIIb/IIIa, total PLT); the effect of urine on activation on PLT was also investigated. The number of activated PLT and the ratio of activated PLT to total PLT in urinary sediments were significantly higher in children with IgAN with diffuse mesangial proliferation than in those with TBMD or MCNS. PLT were activated by addition of urine in 13 out of 27 children with IgAN, and the activity was higher in the urine of those with active glomerular or interstitial lesions, while the urine of children with TBMD or MCNS had no effect. The presence of activated PLT and the effect of urine on PLT activation may be associated with the active glomerular or interstitial lesions in IgAN.


[Treatment adherence in the recurrent depressive disorders].
It is difficult to achieve treatment compliance in recurrent depressive disorders. This disease involves a combination of psychiatric and depressive disorders and is a chronic condition: all of the characteristic features of the disease constitute an obstacle to compliance. Compliance in depressive patients may be improved through various approaches. Information provided to patients, which is widely encouraged today both by doctors and by the regulatory authorities, must be as complete as possible; it must include discussion of factors of that favor depression, as well as the logical basis of the management approach proposed. Furthermore, the best guarantee of compliance is probably maintenance of euthymia by means of suitable treatment. Long-term therapy with antidepressants and the institution of a mood regulator (valproate in particular) have both been shown to be efficacious and significantly superior to placebo. Published studies show that continued treatment with an antidepressant can reduce the risk of depressive relapse noted during long-term follow-up (between 18 months and 5 years) by at least 50%. This has been demonstrated for both tricyclic antidepressants and specific serotonin reuptake inhibitors. The need for continued long-term administration of the dosages with proven efficacy during the acute episode has been demonstrated for imipramine but also appears to have been verified for SSRIs. Even when depressive relapse occurs, it is often less severe if the antidepressant treatment has been continued. Although first-line preventive therapy generally comprises long-term continued administration of the antidepressant, use of mood regulators may occasionally be proposed: valproic acid is generally preferred over lithium assaults on the ground of safety. However, there are few studies demonstrating the preventive efficacy of structured psychotherapy against recurrence of depression. Good treatment compliance entails major benefits: the prescribed treatment is able to reduce the risk of recurrence of depression, and in all probability also reduces subsequent vulnerability to depression, even after treatment discontinuation, as emphasized by the kindling theory of R. Post.


Focal cortical dysplasia of Taylor, balloon cell subtype: MR differentiation from low-grade tumors.
To test the hypothesis that focal cortical dysplasia of Taylor (FCDT) can be distinguished from low-grade tumors by means of clinical and MR findings. We examined 10 clinical and 19 MR imaging variables in patients who underwent surgery for intractable epilepsy over an 8-year period. The 54 patients with low-grade glial neoplasms were compared with the eight patients who had balloon cell FCDT. Statistically significant differences were seen with respect to eight of the MR variables and none of the clinical variables. MR findings suggesting dysplasia rather than tumor included the presence of gray matter thickening associated with a homogeneous hyperintense signal in the subcortical white matter that tapers as it extends to the lateral ventricle. A frontal lobe location favors dysplasia, while a temporal lobe (especially medial temporal lobe) location is more suggestive of a neoplasm. Several MR features help distinguish balloon cell FCDT from neoplasms, especially cortical thickening and a tapered signal to the ventricle. This distinction is important for surgical planning, as the decision to operate and the extent of surgical resection often depend on the presence or absence of neoplastic tissue.


Composition, variability, and temporal stability of the intestinal microbiota of the elderly.
Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.


Percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections.
Operative drainage is the cornerstone of therapy for pancreatic abscess. Recently it has been suggested that successful percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections may serve as definitive therapy. We undertook therapeutic, computed tomography-directed percutaneous drainage in a selected group of 29 patients with infected pancreatic and peripancreatic fluid collections. Twenty-three patients (79%) were successfully treated with percutaneous drainage. Of six patients (21%) representing failures of percutaneous drainage, four died and two recovered after operative drainage. The four patients who died had a mean APACHE (acute physiology and chronic health evaluation) II score of 23 and five of Ranson's prognostic signs. Ranson's signs and APACHE II scores were predictive of success and mortality. We conclude that in selected patients, infected pancreatic and peripancreatic fluid collections can be treated definitively with therapeutic percutaneous catheter drainage. Based on this experience, recommendations regarding patient selection are included.


Partial thrombosis of the false lumen in patients with acute type B aortic dissection.
Patency or thrombosis of the false lumen in type B acute aortic dissection has been found to predict outcomes. The prognostic implications of partial thrombosis of the false lumen have not yet been elucidated. We examined 201 patients with type B acute aortic dissection who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2003 and who survived to hospital discharge. Kaplan-Meier mortality curves were stratified according to the status of the false lumen (patent, partial thrombosis, or complete thrombosis) as determined during the index hospitalization. Cox proportional-hazards analysis was performed to identify independent predictors of death. During the index hospitalization, 114 patients (56.7%) had a patent false lumen, 68 patients (33.8%) had partial thrombosis of the false lumen, and 19 (9.5%) had complete thrombosis of the false lumen. The mean (+/-SD) 3-year mortality rate for patients with a patent false lumen was 13.7+/-7.1%, for those with partial thrombosis was 31.6+/-12.4%, and for those with complete thrombosis was 22.6+/-22.6% (median follow-up, 2.8 years; P=0.003 by the log-rank test). Independent predictors of postdischarge mortality were partial thrombosis of the false lumen (relative risk, 2.69; 95% confidence interval [CI], 1.45 to 4.98; P=0.002), a history of aortic aneurysm (relative risk, 2.05; 95% CI, 1.07 to 3.93; P=0.03), and a history of atherosclerosis (relative risk, 1.87; 95% CI, 1.01 to 3.47; P=0.05). Mortality is high after discharge from the hospital among patients with type B acute aortic dissection. Partial thrombosis of the false lumen, as compared with complete patency, is a significant independent predictor of postdischarge mortality in these patients.


Point-by-point fiber Bragg grating inscription in free-standing step-index and photonic crystal fibers using near-IR femtosecond laser.
We report what we believe to be the first highly symmetric first-order IR femtosecond laser fiber Bragg gratings within the telecommunications C band in free-standing optical fiber, fabricated with a relatively low NA lens and without use of oil immersion techniques. This grating features the smallest dimensions for a point-by-point fiber grating reported so far (to our knowledge). This achievement paves the way to rapid mass manufacturing of highly efficient and stable Bragg gratings using ultrafast lasers in any type of fiber. Mastering this femtosecond grating inscription technique also allowed the fabrication of the first Bragg gratings with direct near-IR femtosecond inscription in photonic crystal fibers, and without the use of techniques that rely on the compensation of the holey structure.


Nocardiosis in renal transplant patients.
Renal transplant patients are immunosuppressed and are at increased risk of opportunistic infections, including Nocardia infection. In renal transplant patients, information on the incidence and risk factors associated with nocardiosis is limited. To address the incidence and risk factors associated with nocardiosis in a large renal transplant population, we used the US Renal Data System (USRDS). Sequelae of allograft failure or rejection after infection were also examined. Demographics, clinical risk factors, Nocardia diagnosis, and allograft failure following Nocardia infection were queried in USRDS renal transplant patients using International Classification of Diseases, Ninth Revision (ICD-9) codes in billing claims and Centers for Medicare and Medicaid Services Form 2728. Generalized linear models were used to determine the risk factors associated with nocardiosis, and Cox proportional hazards models were used to examine the association of risk factors with graft failure among patients with Nocardia infection. Of 203,233 renal transplant recipients identified from 2001 to 2011, 657 (0.32%) were diagnosed with Nocardia infection. Pneumonia was the most frequent presentation (15.2%), followed by brain abscess (8.4%). Numerous factors associated with increased Nocardia infection included age >65 years (OR=2.10, 95% CI 1.71 to 2.59), history of transplant failure (OR=1.28, CI 1.02 to 1.60) or history of rejection (OR=4.83, CI 4.08 to 5.72), receipt of a deceased donor transplant (OR=1.23, CI 1.03 to 1.46), and treatment with basiliximab (OR=1.25, CI 1.00 to 1.55), cyclosporine (OR=1.30, CI 1.03 to 1.65), tacrolimus (OR=2.45, CI 2.00 to 3.00), or thymoglobulin (OR=1.89, CI 1.59 to 2.25). In patients with nocardiosis administration of antithymocyte globulin (HR=2.76), chronic obstructive pulmonary disease (HR=2.47), and presentation of Nocardia infection with brain abscess (HR=1.85) were associated with an increased risk of graft failure. This study provides new information to enhance early recognition and targeted treatment of nocardiosis in renal transplant patients.


Dorsal spinocerebellar tract: response pattern of nerve fibers to muscle stretch.
The response to muscle stretch of second-order neurons of the dorsal spinocerebellar tract was studied in anesthetized cats. Three different types of neurons are defined; the response of each type is remarkably similar to that of the corresponding stretch-receptors of the muscle. Accordingly, the cerebellum receives information on the mechanical situation in muscle from three qualitatively different channels: one has a high degree of sensitivity to dynamic stretch (Ia units) and provides a mixed signal of muscle length and speed of movement; another provides information mainly on muscle length (group-Il units); and the third signals information on the degree of contraction of the muscle (Ib units).


Estimating population genetic parameters and comparing model goodness-of-fit using DNA sequences with error.
It is known that sequencing error can bias estimation of evolutionary or population genetic parameters. This problem is more prominent in deep resequencing studies because of their large sample size n, and a higher probability of error at each nucleotide site. We propose a new method based on the composite likelihood of the observed SNP configurations to infer population mutation rate theta = 4N(e)micro, population exponential growth rate R, and error rate epsilon, simultaneously. Using simulation, we show the combined effects of the parameters, theta, n, epsilon, and R on the accuracy of parameter estimation. We compared our maximum composite likelihood estimator (MCLE) of theta with other theta estimators that take into account the error. The results show the MCLE performs well when the sample size is large or the error rate is high. Using parametric bootstrap, composite likelihood can also be used as a statistic for testing the model goodness-of-fit of the observed DNA sequences. The MCLE method is applied to sequence data on the ANGPTL4 gene in 1832 African American and 1045 European American individuals.


Anterior Cervical Discectomy and Fusion.
Anterior cervical discectomy and fusion can be performed for a variety of pathologies but is most commonly used for the treatment of cervical radiculopathy or myelopathy. The procedure involves an anterior decompression of the disc space followed by interbody grafting and fusion. Supplemental anterior plating is commonly performed, and in certain circumstances, posterior instrumentation may provide additional fixation. The procedure includes the following steps: (1) The use of an anterior approach to the cervical spine, most commonly the Smith-Robinson approach medial to the sternocleidomastoid muscle and the carotid sheath. (2) Confirmation of the proper spinal level. (3) Elevation of the longus colli muscle, which acts as a cuff for the placement of retractors. (4) Removal of the involved disc and decompression of the spinal cord and nerve roots. This is facilitated by disc space distraction, most commonly via distraction pins. Osteophytes along the floor of the spinal canal impinging on the spinal cord are removed with a burr. Soft disc and anular material are also removed, usually with curets and rongeurs. Uncovertebral osteophyte resection and foraminotomies are completed to decompress the exiting nerve roots. (5) Carpentry and decortication of the end plates in preparation for fusion. (6) Sizing of the disc space followed by insertion of an interbody graft. (7) Anterior fixation, most commonly via application of a plate-and-screw construct. (8) Hemostasis and closure.


Threshold of stimulated Brillouin scattering by use of a solar pumped laser.
What is to our knowledge the first stimulated Brillouin scattering experiment using a high-power low-gain solar pumped laser is presented. A threshold reflectivity of 0.23% was reached when a peak power of 20.7 kW was used at 7.6 GHz. A cw solar pumped laser was Q-switched with an acousto-optic modulator, and the bandwidth was narrowed with an intracavity etalon. A high polarization ratio (>99.4%) was achieved by use of an intracavity configuration. Higher reflectivity values were limited because of the lack of availability of optical switches.


Multiple actions of substance P that regulate the functional properties of acetylcholine receptors of clonal rat PC12 cells.
1. The effects of substance P (SP) on each of the kinetic components of reversible desensitization (measured at 4 degrees C) and also on irreversible deactivation (measured at 22 degrees C) of the nicotinic acetylcholine receptor on PC12 cells were examined by 22Na+ influx measurements of the functional state of the receptor. 2. In the absence of agonists, SP converts the acetylcholine receptors in a time- and concentration-dependent manner, to a state that is not responsive to agonist. Upon removal of the peptide, this effect was reversible and the kinetics of the recovery of the permeability response were analysed to provide further characterization of the non-responsive state. Following exposure of cells to SP (10 microM) for 3 or more min, recovery was by a first-order process (time constant, t1/2 = 2.1 min), the same value, within experimental error, as that observed for recovery measured after the initial rapid phase of agonist-mediated desensitization. 3. In the presence of agonist, SP caused a strong enhancement of both the rate and extent of agonist-mediated desensitization. This effect was observed even at concentrations of peptide which produced only a small extent of desensitization when incubated alone. For 500 microM-carbamylcholine, the equilibrium level of desensitization (approximately 85% loss of the permeability response) was achieved at 4 degrees C in about 20 min by a biphasic process, while in the presence of 1.0 microM-SP, complete (100%) desensitization occurred by a single rapid exponential phase characterized by a t1/2 of 20 s. 4. The concentration of carbamylcholine required to produce half-maximal desensitization at equilibrium, Kdes, was 94 microM and was reduced by 6-fold in the presence of 0.3 microM-SP. 5. A mechanistic model is presented in which the receptor is viewed as existing in a dynamic conformational equilibrium between an activatable state Rc and the initial desensitized state Rd. It is proposed that SP binds preferentially to the Rd state and thus can allosterically (1) stabilize the receptor in the absence of agonist in that state, and (2) enhance, in an even lower concentration range, both the rate and extent of agonist-mediated stabilization of the receptor in the Rd state. 6. The second, slower component of agonist-mediated desensitization is, in contrast, inhibited by SP. This desensitization step appears to involve a covalent modification of the initial desensitized state (Rd) and is dependent on Ca2+. SP may exert this inhibitory effect by limiting the access of Ca2+ to an intracellular site of action.(ABSTRACT TRUNCATED AT 400 WORDS)


[Primary linitis plastica carcinoma of the colon and the rectum. Report of three personal cases (author's transl)].
Primary linitis plastica carcinoma of the colon is rare. Only 19 cases have previously been described in the american literature and three french cases are reported. Clinically, this entity appears as an inflammatory lesion. It revolves to a stenotic lesion and death by metastases. Eighty-four per cent of carcinomas are beyond the splenic angle and sixty-six per cent are localized on rectum or distal sigmoid. These tumours are accessible to rectoscopic examination and biopsy which is the only examination able to assert the diagnosis of linitis. Histologically, nothing can distinguish a primary colonic localization from a metastasis. Therefore, it is very important to search for a primary localization especially gastric. Surgical resection is efficient with or without X ray-therapy as we have seen it with control of carcino-embryogenic antigene evolution in one of our cases. Prognosis is bad, especially among people over 50 years with metastasis.


Multidrug-resistant bacteria in geriatric clinics, nursing homes, and ambulant care--prevalence and risk factors.
Colonization/infection with multidrug-resistant bacteria (MDRB) such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, is an increasing problem not only in hospitals but also in long-term care facilities. The aim of this study was to determine the prevalence as well as the risk factors of colonization/infection with MRSA, VRE, and ESBL producing Enterobacteriaceae in geriatric clinics, nursing homes, and ambulant care in Frankfurt am Main, Germany. 288 patients from 2 geriatric clinics (n=46), 8 nursing homes (n=178), and 2 ambulant care facilities (n=64) as well as 64 staff members were screened for MDRB in the time period from October 2006 to May 2007. 58 patients (20.1%) and 4 staff members (6.2%) were colonized with MDRB. Among patients, 27 (9.4%) were colonized with MRSA, 11 (3.8%) were screened positive for VRE, and 25 (8.7%) were found to be colonized with ESBL producing Enterobacteriaceae. Prevalence of MDRB in geriatric clinics, nursing homes, and ambulant care facilities were 32.6%, 18.5%, and 15.6%, respectively. Significant risk factors for MDRB were immobility (OR: 2.7, 95% CI: 1.5-4.9; p=0.002), urinary catheter (OR: 3.1, 95% CI: 1.7-5.9; p<0.001), former hospitalization (OR: 2.1, 95% CI: 1.1-4.0; p=0.033), and wounds/decubiti (OR: 2.3, 95% CI: 1.5-4.9; p=0.03). Finally, the high level of MDRB in geriatric clinics, nursing homes, and ambulant care points to the importance of these institutions as a reservoir for dissemination.


The efficacy of peer assessment in objective structured clinical examinations for formative feedback: a preliminary study.
We sought to determine the impact of medical students' prior experience of assessing peers in the objective structured clinical examination (OSCE) on their clinical performance. Forty-two year 4 medical students participated in an OSCE comprised of three 10-minute stations (syncope, hemoptysis, and back pain). Each student took part in two iterations of the three-station OSCE as either the examiner or examinee, and student performance was assessed using a checklist by a medical faculty member and a student simultaneously. Students were randomly assigned to two groups and their OSCE scores were compared. Students in the control group were tested at a station first and then participated at the same station as a peer examiner, and those in the intervention group participated as a peer examiner first and then as an examinee. Moreover, student OSCE scores rated by peer examiners were compared with those awarded by faculty to evaluate the accuracy of peer assessment. Following the test, students completed surveys on their perceptions of the usefulness of this formative OSCE. Student overall OSCE scores did not differ between groups. Students in the study group performed better at the hemoptysis station (p<0.001), but poorer at the syncope station (p<0.01). Student performances at the back-pain station were similar in these two groups (p=0.48). OSCE scores rated by faculty and peer examiners were moderately negatively associated at the hemoptysis station (p<0.05), but no such association was observed at the other two stations. This trend was similar in peer examiners who were high-achievers and low-achievers in OSCEs. Students showed positive perceptions of their experience with this OSCE. Student experience as peer assessor offers a feasible means of providing them greater access to OSCEs without consuming more resources, although its impact on enhancing performance in the OSCE is likely to differ across stations.